Social health and subsequent cognitive functioning in people aged 50 years and older: examining the mediating roles of depressive symptoms and inflammatory biomarkers in two European longitudinal studies.

BACKGROUND: Social health markers, including marital status, contact frequency, network size, and social support, have been shown to be associated with cognition. However, the mechanisms underlying these associations remain poorly understood. We investigated whether depressive symptoms and inflammation mediated associations between social health and subsequent cognition. METHODS: In the English Longitudinal Study of Ageing (ELSA), a nationally representative longitudinal study in England, UK, we sampled 7136 individuals aged 50 years or older living in private households without dementia at baseline or at the intermediate mediator assessment timepoint, who had recorded information on at least one social health marker and potential mediator. We used four-way decomposition to examine to what extent depressive symptoms, C-reactive protein, and fibrinogen mediated associations between social health and subsequent standardised cognition (verbal fluency and delayed and immediate recall), including cognitive change, with slopes derived from multilevel models (12-year slope). We examined whether findings were replicated in the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a population-based longitudinal study in Sweden, in a sample of 2604 individuals aged 60 years or older living at home or in institutions in Kungsholmen (central Stockholm) without dementia at baseline or at the intermediate mediator assessment timepoint (6-year slope). Social health exposures were assessed at baseline, potential mediators were assessed at an intermediate timepoint (wave 2 in ELSA and 6-year follow-up in SNAC-K); cognitive outcomes were assessed at a single timepoint (wave 3 in ELSA and 12-year follow-up in SNAC-K), and cognitive change (between waves 3 and 9 in ELSA and between 6-year and 12-year follow-ups in SNAC-K). FINDINGS: The study sample included 7136 participants from ELSA, of whom 3962 (55·5%) were women and 6934 (97·2%) were White; the mean baseline age was 63·8 years (SD 9·4). Replication analyses included 2604 participants from SNAC-K, of whom 1604 (61·6%) were women (SNAC-K did not collect ethnicity data); the mean baseline age was 72·3 years (SD 10·1). In ELSA, we found indirect effects via depressive symptoms of network size, positive support, and less negative support on subsequent verbal fluency, and of positive support on subsequent immediate recall (pure indirect effect [PIE] 0·002 [95% CI 0·001-0·003]). Depressive symptoms also partially mediated associations between less negative support and slower decline in immediate recall (PIE 0·001 [0·000-0·002]) and in delayed recall (PIE 0·001 [0·000-0·002]), and between positive support and slower decline in immediate recall (PIE 0·001 [0·000-0·001]). We did not observe mediation by inflammatory biomarkers. Findings of mediation by depressive symptoms in the association between positive support and verbal fluency and between positive support and change in immediate recall were replicated in SNAC-K. INTERPRETATION: The findings of this study provide new insights into mechanisms linking social health with cognition, suggesting that associations between interactional aspects of social health, especially social support, and cognition are partly underpinned by depressive symptoms. FUNDING: EU Joint Programme-Neurodegenerative Disease Research (JPND) and Alzheimer's Society. TRANSLATION: For the Swedish translation of the abstract see Supplementary Materials section.

Somatic disease burden and depression risk in late life: a community-based study.

AIMS: Co-occurring somatic diseases exhibit complex clinical profiles, which can differentially impact the development of late-life depression. Within a community-based cohort, we aimed to explore the association between somatic disease burden, both in terms of the number of diseases and their patterns, and the incidence of depression in older people. METHODS: We analysed longitudinal data of depression- and dementia-free individuals aged 60+ years from the population-based Swedish National Study on Aging and Care in Kungsholmen. Depression diagnoses were clinically ascertained following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision over a 15-year follow-up. Somatic disease burden was assessed at baseline through a comprehensive list of chronic diseases obtained by combining information from clinical examinations, medication reviews and national registers and operationalized as (i) disease count and (ii) patterns of co-occurring diseases from latent class analysis. The association of somatic disease burden with depression incidence was investigated using Cox models, accounting for sociodemographic, lifestyle and clinical factors. RESULTS: The analytical sample comprised 2904 people (mean age, 73.2 [standard deviation (SD), 10.5]; female, 63.1%). Over the follow-up (mean length, 9.6 years [SD, 4 years]), 225 depression cases were detected. Each additional disease was associated with the occurrence of any depression in a dose-response manner (hazard ratio [HR], 1.16; 95% confidence interval [CI]: 1.08, 1.24). As for disease patterns, individuals presenting with sensory/anaemia (HR, 1.91; 95% CI: 1.03, 3.53), thyroid/musculoskeletal (HR, 1.90; 95% CI: 1.06, 3.39) and cardiometabolic (HR, 2.77; 95% CI: 1.40, 5.46) patterns exhibited with higher depression hazards, compared to those without 2+ diseases (multimorbidity). In the subsample of multimorbid individuals (85%), only the cardiometabolic pattern remained associated with a higher depression hazard compared to the unspecific pattern (HR, 1.71; 95% CI: 1.02, 2.84). CONCLUSIONS: Both number and patterns of co-occurring somatic diseases are associated with an increased risk of late-life depression. Mental health should be closely monitored among older adults with high somatic burden, especially if affected by cardiometabolic multimorbidity.

Living Longer But Frailer? Temporal Trends in Life Expectancy and Frailty in Older Swedish Adults.

BACKGROUND: This study aims to examine temporal trends in frailty state transitions, and years spent frail, in older Swedish adults. METHODS: We followed the Swedish National Study on Aging and Care in Kungsholmen participants from baseline (2001-2004) for 15 (median: 9.6) years. A 40-deficit frailty index (FI) was constructed to identify 3 frailty states: robust (FI ≤ 0.125), mild frailty (0.125 < FI ≤ 0.25), and moderate and severe frailty (FI  > 0.25). Multistate survival analyses were implemented to obtain hazard ratios (HRs) for frailty state transitions, with birth year and sex as predictors. To examine temporal trends, frailty state-specific life expectancies at age 60 were forecasted for robust persons born in different years (1900, 1910, 1920, 1930, and 1940), also by sex. RESULTS: At baseline, the 2 941 participants' mean age was 75 years and 65% were women. Predicted life expectancy and time spent frail from age 60 followed an increasing trend by birth year. Hazards of transitioning from mild frailty to death (HR: 0.89; 95% confidence interval [CI]: 0.83-0.97) and moderate and severe frailty to death (HR: 0.98; 95% CI: 0.97-1.00) were lower for those born later. Women were less likely to transition from robust to mild frailty (HR: 0.81; 95% CI: 0.70-0.93), mild frailty to moderate and severe frailty (HR: 0.80; 95% CI: 0.68-0.93), and moderate and severe frailty to death (HR: 0.68; 95% CI: 0.59-0.78), but spent more time frail. CONCLUSIONS: Our results point to an expansion of time spent frail among older Swedish adults over time.

Early growth, stress, and socioeconomic factors as predictors of the rate of multimorbidity accumulation across the life course: a longitudinal birth cohort study.

BACKGROUND: Early growth, stress, and socioeconomic factors are associated with future risk of individual chronic diseases. It is uncertain whether they also affect the rate of multimorbidity accumulation later in life. This study aimed to explore whether early life factors are associated with the rate at which chronic diseases are accumulated across older age. METHODS: In this national birth cohort study, we studied people born at Helsinki University Central Hospital, Helsinki, Finland between Jan 1, 1934, and Dec 31, 1944, who attended child welfare clinics in the city, and were living in Finland in 1971. Individuals who had died or emigrated from Finland before 1987 were excluded, alongside participants without any registry data and who died before the end of the registry follow-up on Dec 31, 2017. Early anthropometry, growth, wartime parental separation, and socioeconomic factors were recorded from birth, child welfare clinic, or school health-care records, and Finnish National Archives. International Classification of Diseases codes of diagnoses for chronic diseases were obtained from the Care Register for Health Care starting from 1987 (when participants were aged 42-53 years) until 2017. Linear mixed models were used to study the association between early-life factors and the rate of change in the number of chronic diseases over 10-year periods. FINDINGS: From Jan 1, 1934, to Dec 31, 2017, 11 689 people (6064 [51·9%] men and 5625 [48·1%] women) were included in the study. Individuals born to mothers younger than 25 years (ß 0·09; 95% CI 0·06-0·12), mothers with a BMI of 25-30 kg/m2 (0·08; 0·05-0·10), and mothers with a BMI more than 30 kg/m2 (0·26; 0·21-0·31) in late pregnancy accumulated chronic diseases faster than those born to older mothers (25-30 years) and those with a BMI of less than 25 kg/m2. Individuals with a birthweight less than 2·5 kg (0·17; 0·10-0·25) and those with a rapid growth in height and weight from birth until age 11 years accumulated chronic diseases faster during their life course. Additionally, paternal occupational class (manual workers vs upper-middle class 0·27; 0·23-0·30) and wartime parental separation (0·24; 0·19-0·29 for boys; 0·31; 0·25-0·36 for girls) were associated with a faster rate of chronic disease accumulation. INTERPRETATION: Our findings suggest that the foundation for accumulating chronic diseases is established early in life. Early interventions might be needed for vulnerable populations, including war evacuee children and children with lower socioeconomic status. FUNDING: Finska Läkaresällskapet, Liv och Hälsa rf, the Finnish Pediatric Research Foundation, and Folkhälsan Research Center. TRANSLATIONS: For the Finnish and Swedish translations of the abstract see Supplementary Materials section.

Association of Lifelong Cognitive Reserve with Dementia and Mild Cognitive Impairment among Older Adults with Limited Formal Education: A Population-Based Cohort Study.

INTRODUCTION: Early-life educational attainment contributes to cognitive reserve (CR). We investigated the associations of lifelong CR with dementia and mild cognitive impairment (MCI) among older people with limited formal education. METHODS: This population-based cohort study included 2,127 dementia-free participants (≥60 years; 59.4% women; 81.5% with no or elementary school) who were examined at baseline (August-December 2014) and follow-up (March-September 2018). Lifelong CR score at baseline was generated from six lifespan intellectual factors. Dementia, MCI, and their subtypes were defined according to the international criteria. Data were analyzed using Cox proportional-hazards models. RESULTS: During the total of 8,330.6 person-years of follow-up, 101 persons were diagnosed with dementia, including 74 with Alzheimer's disease (AD) and 26 with vascular dementia (VaD). The high (vs. low) tertile of lifelong CR score was associated with multivariable-adjusted hazards ratios (95% confidence interval) of 0.28 (0.14-0.55) for dementia and 0.18 (0.07-0.48) for AD. The association between higher CR and reduced AD risk was significant in people aged 60-74 but not in those aged ≥75 years (p for interaction = 0.011). Similarly, among MCI-free people at baseline (n = 1,635), the high (vs. low) tertile of lifelong CR score was associated with multivariable-adjusted hazard ratios of 0.51 (0.38-0.69) for MCI and 0.46 (0.33-0.64) for amnestic MCI. Lifelong CR was not related to VaD or non-amnestic MCI. DISCUSSION: High lifelong CR is associated with reduced risks of dementia and MCI, especially AD and amnestic MCI. It highlights the importance of lifelong CR in maintaining late-life cognitive health even among people with no or limited education.

Social Health and Change in Cognitive Capability among Older Adults: Findings from Four European Longitudinal Studies.

INTRODUCTION: In this study, we examine whether social health markers measured at baseline are associated with differences in cognitive capability and the rate of cognitive decline over an 11-to-18-year period among older adults and compare results across studies. METHODS: We applied an integrated data analysis approach to 16,858 participants (mean age 65 years; 56% female) from the National Survey for Health and Development (NSHD), the English Longitudinal Study of Aging (ELSA), the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), and the Rotterdam Study. We used multilevel models to examine social health in relation to cognitive capability and the rate of cognitive decline. RESULTS: Pooled estimates show distinct relationships between markers of social health and cognitive domains, e.g., a large network size (≥6 people vs. none) was associated with higher executive function (0.17 standard deviation [SD] [95% CI: 0.00, 0.34], I2 = 27%) but not with memory (0.08 SD [95% CI: -0.02, 0.18], I2 = 19%). We also observed pooled associations between being married or cohabiting, having a large network size, and participating in social activities with slower decline in cognitive capability. However, estimates were close to zero, e.g., 0.01 SD/year (95% CI: 0.01, 0.02) I2 = 19% for marital status and executive function. There were clear study-specific differences: results for average processing speed were the most homogenous, and results for average memory were the most heterogeneous. CONCLUSION: Overall, markers of good social health have a positive association with cognitive capability. However, we found differential associations between specific markers of social health and cognitive domains and differences between studies. These findings highlight the importance of examining between-study differences and considering the context specificity of findings in developing and deploying interventions.

Trajectories of Physical Function and Behavioral, Psychological, and Social Well-Being in a Cohort of Swedish Older Adults.

Background and Objectives: Successful aging has been described as a multifactorial and dynamic process. The aims of the study were to detect aging trajectories of physical function and behavioral, psychological, and social well-being; and to explore the correlations between functional versus well-being trajectories by age group. Research Design and Methods: Data were gathered from the Swedish National Study on Aging and Care in Kungsholmen (N = 1,375). Subjects' physical function was assessed through walking speed and chair-stand tests, behavioral well-being through participation in mental and physical activities, psychological well-being through life satisfaction and positive affect, and social well-being through social connections and support. All exposures were standardized (z-scores). Linear mixed models were used to estimate trajectories of physical function and well-being over a 12-year follow-up. Results: The steepest declines were seen for physical function (relative change [RC] in z-scores across ages; RC = 3.01), followed by behavioral well-being (RC = 2.15), psychological well-being (RC = 2.01), and social well-being (RC = 0.76). Correlations between physical function and the different well-being domains were weak, especially for slopes. Stronger intercept correlations were observed among the oldest-compared to the youngest-old, especially with behavioral (r = 0.39 vs r = 0.24) and psychological (r = 0.33 vs r = 0.22) well-being. Discussion and Implications: Physical function declines the fastest throughout aging. The different well-being domains decline at a slower rate, which may be a possible sign of compensation against age-related functional decline, especially among the youngest-old, for whom discordances between physical function and the different well-being domains were more common.

Association between personality traits, leisure activities, and cognitive levels and decline across 12 years in older adults.

The engagement in cognitively stimulating activities has been found to be associated with slower rates of cognitive decline in old age. In which type of activities people engage in may depend on their personality traits, which thus might have an impact on later cognitive fitness. To study these potential links, we examined the associations between Neuroticism, Extraversion, and Openness; different types of leisure activities (e.g., social, mental, physical); and cognitive ability levels and decline in older adults. Analyses were based on a sample of young-old (60-72 years old; n = 1,609) and old-old (78 years or older; n = 1,085) adults from the Swedish National Study on Aging and Care in Kungsholmen, who participated in up to five repeated measurements of cognitive abilities spanning 12 years. We used latent growth curve models to estimate cognitive levels and decline, as well as the correlations with initial personality trait levels and leisure activity engagement. In both groups, lower Neuroticism, higher Extraversion, and higher Openness levels were moderately associated with stronger engagement in all types of activities. Lower Neuroticism, higher Extraversion, and a more activity lifestyle were weakly to moderately associated with slower cognitive decline in the old-old age group. There, personality traits and activities explained 9.3% of the variance in cognitive decline after controlling for age, sex, education, and chronic diseases (which explained 9.0%). Taken together, this study provides further evidence for the connection between personality traits, activity engagement, and later cognitive decline in old age. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Socioeconomic differences in older adults' unplanned hospital admissions: the role of health status and social network.

BACKGROUND: the socioeconomic distribution of unplanned hospital admissions in older adults is poorly understood. We compared associations of two life-course measures of socioeconomic status (SES) with unplanned hospital admissions while comprehensively accounting for health, and examined the role of social network in this association. METHODS: in 2,862 community-dwelling adults aged 60+ in Sweden, we derived (i) an aggregate life-course SES measure grouping individuals into Low, Middle or High SES based on a summative score, and (ii) a latent class measure that additionally identified a Mixed SES group, characterised by financial difficulties in childhood and old age. The health assessment combined measures of morbidity and functioning. The social network measure included social connections and support components. Negative binomial models estimated the change in hospital admissions over 4 years in relation to SES. Stratification and statistical interaction assessed effect modification by social network. RESULTS: adjusting for health and social network, unplanned hospitalisation rates were higher for the latent Low SES and Mixed SES group (incidence rate ratio [IRR] = 1.38, 95% confidence interval [CI]: 1.12-1.69, P = 0.002; IRR = 2.06, 95% CI: 1.44-2.94, P < 0.001; respectively; ref: High SES). Mixed SES was at a substantially greater risk of unplanned hospital admissions among those with poor (and not rich) social network (IRR: 2.43, 95% CI: 1.44-4.07; ref: High SES), but the statistical interaction test was non-significant (P = 0.493). CONCLUSION: socioeconomic distributions of older adults' unplanned hospitalisations were largely driven by health, although considering SES dynamics across life can reveal at-risk sub-populations. Financially disadvantaged older adults might benefit from interventions aimed at improving their social network.

Late-life depression and multimorbidity trajectories: the role of symptom complexity and severity.

INTRODUCTION: as late-life depression is associated with poor somatic health, we aimed to investigate the role of depression severity and symptom phenotypes in the progression of somatic multimorbidity. METHODS: we analysed data from 3,042 dementia-free individuals (60+) participating in the population-based Swedish National Study on Aging and Care in Kungsholmen. Using the baseline clinical assessment of 21 depressive symptoms from the Comprehensive Psychopathological Rating Scale, we: (i) diagnosed major, minor (in accordance with DSM-IV-TR) and subsyndromal depression; (ii) extracted symptom phenotypes by applying exploratory network graph analysis. Somatic multimorbidity was measured as the number of co-occurring chronic diseases over a 15-year follow-up. Linear mixed models were used to explore somatic multimorbidity trajectories in relation to baseline depression diagnoses and symptom phenotypes, while accounting for sociodemographic and behavioural factors. RESULTS: in multi-adjusted models, relative to individuals without depression, those with major (ß per year: 0.33, 95% confidence interval [CI]: 0.06-0.61) and subsyndromal depression (ß per year: 0.21, 95%CI: 0.12-0.30) experienced an accelerated rate of somatic multimorbidity accumulation, whereas those with minor depression did not. We identified affective, anxiety, cognitive, and psychomotor symptom phenotypes from the network analysis. When modelled separately, an increase in symptom score for each phenotype was associated with faster multimorbidity accumulation, although only the cognitive phenotype retained its association in a mutually adjusted model (ß per year: 0.07, 95%CI: 0.03-0.10). CONCLUSIONS: late-life major and subsyndromal depression are associated with accelerated somatic multimorbidity. Depressive symptoms characterised by a cognitive phenotype are linked to somatic health change in old age.

Lifelong Cognitive Reserve, Imaging Markers of Brain Aging, and Cognitive Function in Dementia-Free Rural Older Adults: A Population-Based Study.

BACKGROUND: Cognitive reserve (CR) partly explains cognitive variability in the presence of pathological brain aging. OBJECTIVE: We investigated the interplay of lifelong CR with age, sex, and brain aging markers in cognitive phenotypes among older adults with very limited education. METHODS: This population-based cross-sectional study included 179 dementia-free participants (age ≥65 years; 39.7% women; 67.0% had no or elementary education) examined in 2014-2016. We assessed lacunes and volumes of hippocampus, ventricles, grey matter, white matter (WM), and white matter hyperintensities. Lifelong CR score was generated from six lifespan intellectual factors (e.g., education and social support). We used Mini-Mental State Examination (MMSE) score to assess cognition and Petersen's criteria to define mild cognitive impairment (MCI). Data were analyzed using general linear and logistic models. RESULTS: The association of higher lifelong CR score (range: -4.0-5.0) with higher MMSE score was stronger in women (multivariable-adjusted ß-coefficient and 95% CI: 1.75;0.99-2.51) than in men (0.68;0.33-1.03) (pinteraction = 0.006). The association of higher CR with MCI (multivariable-adjusted odds ratio and 95% CI: 0.77;0.60-0.99) did not vary by age or sex. Among participants with low CR (<1.4[median]), greater hippocampal and WM volumes were related to higher MMSE scores with multivariable-adjusted ß-coefficients being 1.77(0.41-3.13) and 0.44(0.15-0.74); the corresponding figures in those with high CR were 0.15(-0.76-1.07) and -0.17(-0.41-0.07) (pinteraction <0.01). There was no statistical interaction of CR with MRI markers on MCI. CONCLUSION: Greater lifelong CR capacity is associated with better late-life cognition among people with limited education, possibly by compensating for impact of neurodegeneration.

Social Health and Cognitive Change in Old Age: Role of Brain Reserve.

OBJECTIVE: Individual aspects of social health (SH; eg, network, engagement, support) have been linked to cognitive health. However, their combined effect and the role of the structural properties of the brain (brain reserve [BR]) remain unclear. We investigated the interplay of SH and BR on cognitive change in older adults. METHODS: Within the Swedish National Study on Aging and Care-Kungsholmen, 368 dementia-free adults aged ≥60 years with baseline brain magnetic resonance imaging were followed over 12 years to assess cognitive change. A measure of global cognition was computed at each of the 5 waves of assessment by averaging domain-specific Z scores for episodic memory, perceptual speed, semantic memory, and letter and category fluency. An SH composite score was computed at baseline by combining leisure activities and social network. BR was proxied by total brain tissue volume (TBTV). Linear mixed models (adjusted for sociodemographic, vascular, and genetic factors) were used to estimate cognitive trajectories in relation to SH and TBTV. Interaction analysis and stratification were used to examine the interplay between SH and TBTV. RESULTS: Moderate-good SH (n = 245; vs poor, ß-slope = 0.01, 95% confidence interval [CI] = 0.002-0.02, p = 0.018) and moderate-to-large TBTV (n = 245; vs small, ß-slope = 0.03, 95% CI = 0.02-0.04, p < 0.001) were separately associated with slower cognitive decline. In stratified analysis, moderate-good SH was associated with higher cognitive levels (but not change) only in participants with moderate-to-large TBTV (ß-intercept = 0.21, 95% CI = 0.06-0.37, p < 0.01; interaction SH * TBTV, p < 0.05). INTERPRETATION: Our findings highlight the interplay between SH and BR that likely unfolds throughout the entire life course to shape old-age cognitive outcomes. ANN NEUROL 2023;93:844-855.

Association Between Behavioral, Biological, and Genetic Markers of Cardiovascular Health and MRI Markers of Brain Aging: A Cohort Study.

BACKGROUND AND OBJECTIVE: The life's simple 7 approach was proposed to define cardiovascular health (CVH) metrics. We sought to investigate the associations between behavioral, biological, and genetic markers for CVH and vascular brain aging in older adults. METHODS: This population-based cohort study included participants who had repeated brain MRI measures from 2001 to 2003 to 2007-2010 (i.e., count of perivascular spaces, volumes of white matter hyperintensity [WMH] and gray matter, and lacunes). At baseline, global, behavioral, and biological CVH metrics were defined and scored following the life's simple 7 approach and categorized into unfavorable, intermediate, and favorable profiles according to tertiles. The metabolic genetic risk score was calculated by counting 15 risk alleles associated with hypertension, diabetes, or dyslipidemia. Data were analyzed using linear mixed-effects and Cox proportional hazards models, adjusting for age, sex, and education. RESULTS: The study sample consisted of 317 participants (age 60 years or older; 61.8% women). Favorable and intermediate (vs unfavorable) global CVH profiles were related to slower WMH progression, with ß-coefficients (95% CI) being -0.019(-0.035-0.002) and -0.018(-0.034-0.001), respectively. Favorable and intermediate (vs unfavorable) biological CVH profiles were significantly related to slower WMH increase only in people aged 60-72 years. CVH profiles were not related to progression of other brain measures. Furthermore, a higher metabolic genetic risk score (range: 6-21) was associated with faster WMH increase (ß-coefficient = 0.005; 95% CI: 0.003-0.008). There were statistical interactions of metabolic genetic risk score with global and behavioral CVH profiles on WMH accumulation. A higher metabolic genetic risk score was related to faster WMH accumulation, with ß-coefficients being 0.015(0.007-0.023), 0.005(0.001-0.009), and 0.003(-0.001 to 0.006) among people with unfavorable, intermediate, and favorable global CVH profiles, respectively; the corresponding ß-coefficients were 0.013(0.006-0.020), 0.006(0.003-0.009), and 0.002(-0.002 to 0.006) among people with unfavorable, intermediate, and favorable behavioral CVH profiles. DISCUSSION: Intermediate to favorable global CVH profiles in older adults are associated with slower vascular brain aging. The association of metabolic genetic risk load with accelerated vascular brain aging was evident among people with unfavorable to intermediate, but not favorable, CVH profiles. These findings highlight the importance of adhering to favorable CVH profiles, especially healthy behaviors, in vascular brain health.

Profiles of behavioral, social and psychological well-being in old age and their association with mobility-limitation-free survival.

INTRODUCTION: Successful aging is a multidimensional construct covering behavioral, social, and psychological domains of well-being. We aimed to identify well-being profiles and their association with mobility-limitation-free survival. METHODS: A total of 1488 healthy individuals aged 60+ from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) were followed-up for 15 years. Mobility limitation was defined as a walking speed <0.8m/s and vital status information was obtained from the National Cause of Death Register. Well-being profiles were derived from different behavioral, social and psychological indicators using latent class analysis among men and women. Cox and Laplace regression models were applied to examine the association with the incidence of a composite endpoint of mobility limitation or death. RESULTS: At baseline, three well-being profiles (i.e., worst, intermediate, best) were identified, which followed a clear gradient in all behavioral, social and psychological indicators. Compared to those in the worst profile, men and women in the intermediate profile had 27% (HR 0.73; 95% CI 0.56-0.94) and 23% (HR 0.77; 95% CI 0.59-1.00) lower hazard of developing mobility limitation/death. An even greater protective effect was seen among individuals in the best versus worst profile (HR 0.47; 95% CI 0.31-0.70 in men; HR 0.60; 95% CI 0.46-0.78 in women). Men in the intermediate and best profiles survived 1 and 3 years longer without mobility limitation, respectively; these figures were 2 and 3 years for women. CONCLUSIONS: Better profiles of behavioral, social and psychological well-being may prolong mobility-limitation-free survival by at least one year among older adults. Our findings strengthen the evidence-base to achieve successful aging through multi-domain interventions.

Pre-pandemic Physical Function and Social Network in Relation to COVID-19-Associated Depressive Burden in Older Adults in Sweden.

Background and Objectives: The coronavirus disease 2019 (COVID-19) pandemic, as well as the measures intended to limit its spread, have likely affected older adults' depressive burden. Good physical functioning and a rich social network may benefit older adults' mental health. We examined whether pre-pandemic physical functioning and social network were associated with depressive burden during the first wave of the COVID-19 pandemic in Stockholm, Sweden. Research Design and Methods: A telephone assessment of depressive burden using the symptoms of sadness, anxiety, worrying, reduced sleep, and reduced appetite was conducted in May-September 2020 in 930 older adults from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), an ongoing population-based study. Objective measures of gait speed, muscle strength, and balance; and self-reports of social connections and support were collected in 2016-2019. Logistic models were adjusted for sociodemographic, clinical, lifestyle, and pandemic-related factors (loneliness, change in physical and social engagement, and experience of death due to COVID-19). Results: Only good muscle strength (odds ratio [OR]: 0.53; 95% confidence interval [CI]: 0.32-0.85; ref: poor strength, ≥17 s) and rich social support (OR: 0.67; 95% CI: 0.45-0.99; ref: poor support) exhibited an independent association with depressive burden, even after accounting for pandemic-related factors. A combination of good muscle strength and rich social support were associated with the greatest reduction in depressive burden (OR: 0.35; 95% CI: 0.18-0.66; ref: poor social support and poor muscle strength). Discussion and Implications: Prepandemic social support and muscle strength could supply older adults with resilience against the depressive burden associated with the COVID-19 pandemic.

Factors associated with physical activity reduction in Swedish older adults during the first COVID-19 outbreak: a longitudinal population-based study.

BACKGROUND: Physical activity (PA) decreased during the COVID-19 pandemic, especially among older adults, potentially leading to adverse consequences for their health. However, factors associated with reductions of PA during the pandemic have not been examined in a population-based sample of older adults. Thus, the aim of this study was to explore the association of pre-pandemic physical, mental, social and lifestyle factors with reductions in PA in older adults during the first wave of COVID-19, and whether the associations differed by age and sex. METHODS: A population-based sample of 624 participants aged 65-99 years were identified from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) COVID19 Study. Information on pre-pandemic factors was collected through clinical examinations, interviews, and self-administered questionnaires in 2016-2019. Changes in light and intense PA during the first wave of the pandemic (May-September 2020) were self-reported. Data were analyzed using multiple logistic regression models, stratified by age (<70 vs. >80 years) and sex. RESULTS: There was an association between pre-pandemic levels of higher depressive symptom burden (Odds Ratio (OR): 2.6, 95% Confidence Interval (CI): 1.1-6.4, <70 years), and impaired balance (OR: 1.7, 95% CI: 1.0-2.8, >80 years old) with reductions in light-intensity PA. Furthermore, the presence of musculoskeletal disease (OR: 1.8, 95% CI: 1.1-2.9, <70 years; OR: 2.3, 95% CI: 1.2-4.4, men), moderate/high levels of neuroticism (OR: 1.6, 95% CI: 1.0-2.6, <70 years; OR: 2.2, 95% CI: 1.3-3.5, women), and poor levels of social support (OR: 2.2, 95% CI: 1.2-4.3, >80 years) were related to reductions in higher-intensity PA. Those who were current smokers (OR: 0.3, 95% CI: 0.1-0.8, <70 years; OR: 0.2, 95% CI: 0.06-0.7, women), or had impaired balance (OR: 0.4, 95% CI: 0.2-0.8, >80 years) were less likely to reduce their levels of higher-intensity PA. CONCLUSIONS: For future pandemics or waves of COVID-19, development of strategies is warranted for older individuals with psychiatric- or physical illness/dysfunction, as well as those with poor social support to counteract reductions in physical activities.

Progression of neuroimaging markers of cerebral small vessel disease in older adults: A 6-year follow-up study.

We investigated progression and interrelationships of cerebral small vessel disease (cSVD) markers. This population-based cohort study included 325 participants (age ≥ 60 years) who had repeated measures of cSVD markers over 6 years: white-matter hyperintensity (WMH), perivascular spaces (PVS), lacunes, and grey-matter (GM) and ventricular volumes. We found that all cSVD markers, except PVS, progressed faster with increasing age. Regional WMH progressed faster in males and less-educated people (p < 0.05). Each 10-point increment in global WMH score was associated with multi-adjusted hazard ratio of 1.78 (95% CI = 1.50‒2.10) for incident lacunes and multi-adjusted ß-coefficients of 0.15 (0.08-0.22), -0.37 (-0.58‒-0.16), and 0.11 (0.03‒0.18) for annual changes of global WMH score, GM volume, and ventricular volume, respectively. The corresponding figures associated with per 10-PVS increment were 1.14 (1.01‒1.28), 0.07 (0.03‒0.11), -0.18 (-0.32‒-0.04), and 0.02 (-0.03‒0.07). Prevalent lacunes were related to multi-adjusted ß-coefficients of 0.29 (0.00‒0.58), 0.22 (0.05‒0.38), 0.10 (0.01‒0.18), and -0.93 (-1.83‒-0.03) for annual changes of global, deep, and periventricular WMH scores and GM volume, respectively. These results suggest that cSVD progresses faster in older, male, and less-educated people, and that greater loads of WMH, PVS, and lacunes anticipate faster cSVD progression.

Bridging late-life depression and chronic somatic diseases: a network analysis.

The clinical presentation of late-life depression is highly heterogeneous and likely influenced by the co-presence of somatic diseases. Using a network approach, this study aims to explore how depressive symptoms are interconnected with each other, as well as with different measures of somatic disease burden in older adults. We examined cross-sectional data on 2860 individuals aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen, Stockholm. The severity of sixteen depressive symptoms was clinically assessed with the Comprehensive Psychopathological Rating Scale. We combined data from individual clinical assessment and health-registers to construct eight system-specific disease clusters (cardiovascular, neurological, gastrointestinal, metabolic, musculoskeletal, respiratory, sensory, and unclassified), along with a measure of overall somatic burden. The interconnection among depressive symptoms, and with disease clusters was explored through networks based on Spearman partial correlations. Bridge centrality index and network loadings were employed to identify depressive symptoms directly connecting disease clusters and depression. Sadness, pessimism, anxiety, and suicidal thoughts were the most interconnected symptoms of the depression network, while somatic symptoms of depression were less interconnected. In the network integrating depressive symptoms with disease clusters, suicidal thoughts, reduced appetite, and cognitive difficulties constituted the most consistent bridge connections. The same bridge symptoms emerged when considering an overall measure of somatic disease burden. Suicidal thoughts, reduced appetite, and cognitive difficulties may play a key role in the interconnection between late-life depression and somatic diseases. If confirmed in longitudinal studies, these bridging symptoms could constitute potential targets in the prevention of late-life depression.

Mobility and muscle strength trajectories in old age: the beneficial effect of Mediterranean diet in combination with physical activity and social support.

INTRODUCTION: Decline in physical function varies substantially across older individuals due to several extrinsic modifiable factors such as dietary patterns, physical activity and social support. We aimed to determine the association of these factors and their interaction with mobility and muscle strength decline. METHODS: We analyzed data from 1686 functionally healthy individuals aged 60 + from the population-based Swedish National study on Aging and Care in Kungsholmen (SNAC-K). The Mediterranean Diet Score (MDS) was calculated based on a validated food frequency questionnaire. Self-reported physical activity was categorized based on current recommendations, and social support was measured according to participants' perceived material and psychological support from relatives and friends. Participants' physical function was assessed over 12 years through changes in walking speed (m/s) and chair stand time (s). Linear mixed models adjusted for socio-demographic and clinical factors were used. In order to explore the combined effect of the different exposures, two indicator variables were created by cross-classifying individuals' levels of Mediterranean diet adherence and social support or physical activity. RESULTS: Participants with a high adherence to Mediterranean diet were primarily < 78 years (82.3%), women (56.1%), married (61.1%), with university education (52.8%), high levels of social support (39.3%) and health-enhancing levels of physical activity (51.5%). A one-point increase in MDS (score range 0-9) was associated with less annual deterioration in walking speed (ß*time[year] = 0.001; p = 0.024) and chair-stand time (ß*time[year] = -0.014; p = 0.008). The potential protective effect of Mediterranean diet was highest among participants reporting high social support (ß*time[year] = -0.065, p = 0.026 for chair stands) and high physical activity (ß*time[year] = 0.010, p = 0.001 for walking speed), beyond the effect of each exposure individually. CONCLUSION: A higher adherence to Mediterranean diet, especially in combination with recommended levels of physical activity and high social support, may contribute to delay the decline in physical function observed with aging.

Cognitive Trajectories and Dementia Risk: A Comparison of Two Cognitive Reserve Measures.

BACKGROUND AND OBJECTIVES: Cognitive reserve (CR) is meant to account for the mismatch between brain damage and cognitive decline or dementia. Generally, CR has been operationalized using proxy variables indicating exposure to enriching activities (activity-based CR). An alternative approach defines CR as residual variance in cognition, not explained by the brain status (residual-based CR). The aim of this study is to compare activity-based and residual-based CR measures in their association with cognitive trajectories and dementia. Furthermore, we seek to examine if the two measures modify the impact of brain integrity on cognitive trajectories and if they predict dementia incidence independent of brain status. METHODS: We used data on 430 older adults aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen, followed for 12 years. Residual-based reserve was computed from a regression predicting episodic memory with a brain-integrity index incorporating six structural neuroimaging markers (white-matter hyperintensities volume, whole-brain gray matter volume, hippocampal volume, lateral ventricular volume, lacunes, and perivascular spaces), age, and sex. Activity-based reserve incorporated education, work complexity, social network, and leisure activities. Cognition was assessed with a composite of perceptual speed, semantic memory, letter-, and category fluency. Dementia was clinically diagnosed in accordance with DSM-IV criteria. Linear mixed models were used for cognitive change analyses. Interactions tested if reserve measures modified the association between brain-integrity and cognitive change. Cox proportional hazard models, adjusted for brain-integrity index, assessed dementia risk. RESULTS: Both reserve measures were associated with cognitive trajectories [ß × time (top tertile, ref.: bottom tertile) = 0.013; 95% CI: -0.126, -0.004 (residual-based) and 0.011; 95% CI: -0.001, 0.024, (activity-based)]. Residual-based, but not activity-based reserve mitigated the impact of brain integrity on cognitive decline [ß (top tertile × time × brain integrity) = -0.021; 95% CI: -0.043, 0.001] and predicted 12-year dementia incidence, after accounting for the brain-integrity status [HR (top tertile) = 0.23; 95% CI: 0.09, 0.58]. INTERPRETATION: The operationalization of reserve based on residual cognitive performance may represent a more direct measure of CR than an activity-based approach. Ultimately, the two models of CR serve largely different aims. Accounting for brain integrity is essential in any model of reserve.